The proposed studies are designed to gain an understanding of the stromal or nonstromal cell types involved in the regulation of hemopoietic stem cells. We will also study the mechanisms by which lithium stimulates murine hemopoiesis at the same time using it as a probe for the study of cellular interactions. Specifically, we first plan to characterize the Dexter in vitro stem cell maintenance culture system. We will isolate populations of cells which will 1) have hemopoietic stem cells, not form stroma but grow on preformed stroma, and 2) which will form stroma but have no stem cells. Once the system is established we will utilize a number of cell separative or culture techniques in conjunction with add-back subtraction experiments to evaluate the role of various subsets of cells in regulating hemopoiesis especially T lymphocytes, monocytes and endothelial cells. With the basic characteristics of these cell interactions determined we will explore the mechanisms by which lithium stimulates hemopoiesis and particularly the pluripotent stem cell, investigating whether this is a direct effect or mediated via effector cells producing "myelokines". The late inhibitory effects of lithium will be investigated in a similar manner and the genetically anemic S1/S1d and W/Wv mice utilized to further characterize the site of action of lithium. Lastly, attempts will be made to establish long-term human Dexter cultures so that studies similar to those described above can be carried out on human cells.